E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MILD ALZHEIMER?S DISEASE |
Enfermedad de Alzheimer Leve |
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E.1.1.1 | Medical condition in easily understood language |
MILD ALZHEIMER?S DISEASE |
Enfermedad de Alzheimer Leve |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to evaluate the efficacy of gantenerumab compared with placebo administered to patients by SC injection over 100 weeks as measured by the following co-primary endpoints (final outcome assessment 4 weeks after the final dose): ? Cognition measured by the Alzheimer?s Disease Activity Scale?Cognitive (ADAS-Cog) (13-item) ? Function assessed by the Alzheimer?s Disease Cooperative Study?Activities of Daily Living (ADCS-ADL) |
Evaluar la eficacia de gantenerumab comparado con placebo, administrado a los pacientes en inyección subcutánea (SC) durante 100 semanas, que se determinará basándose en las covariables principales siguientes (la evaluación del resultado final se realizará 4 semanas después de administrar la última dosis): ? Capacidad cognitiva, valorada mediante la Alzheimer?s Disease Activity Scale?Cognitive (ADAS-Cog) (13 ítems) ? Capacidad funcional, valorada mediante el Alzheimer?s Disease Cooperative Study?Activities of Daily Living (ADCS-ADL) |
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E.2.2 | Secondary objectives of the trial |
1. to evaluate the benefits of gantenerumab versus placebo administered to patients by SC injection over 100 weeks on slowing clinical decline and disease progression by assessing the following: ? Time to clinically evident decline ? Disease pathology biomarkers 2. Additional secondary endpoints · Global: Effect on severity of dementia and global measures of cognition and function · Cognition: Effect on cognition · Behavioar: Effect on behavioral and neuropsychological symptoms of AD · Other AD symptoms and effects: Effect of gantenerumab on health-related QoL, patient-individualized goal achievement (sites in English- and French-speaking countries only), on caregiver emotional well-being, on the amount of assistance patients with dementia require in performing daily activities |
Evaluar beneficios de gantenerumab frente a placebo, administrado a pacientes en inyección SC durante 100 semanas, respecto a retraso de deterioro clínico y la progresión de la enfermedad.Se valorará en base: Tiempo hasta deterioro clínicamente evidente Biomarcadores de patología de la enfermedad Objetivos secundarios adicionales: Medidas globales-Efecto sobre severidad de demencia y medidas globales de capacidad cognitiva y funcional. Capacidad cognitiva-Efecto sobre capacidad cognitiva Síntomas conductuales-Efecto sobre síntomas conductuales y neuropsicológicos de EA Otros síntomas y efectos relacionados con EA: Efecto de gantenerumab sobre calidad de vida relacionada con salud (CVRS), consecución de objetivos individualizados de pacientes (se aplicará sólo en centros de países de habla inglesa y francesa), sobre bienestar emocional del cuidador, sobre cantidad de ayuda que requieren los pacientes con demencia para realizar las actividades diarias |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
WN28745-PET Substudy, version 1, dated 19-Nov-2013
Title: PET IMAGING SUBSTUDY ASSOCIATED WITH: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER, EFFICACY, AND SAFETY STUDY OF GANTENERUMAB IN PATIENTS WITH MILD ALZHEIMER?S DISEASE
The primary objective of the WN28745-PET substudy is to assess changes in amyloid load over time using florbetapir in patients enrolled in Study WN28745 who are treated with gantenerumab (RO4909832) or placebo. This patient population has probable mild AD (based on NINCDS/ADRDA criteria) or probable major NCD due to AD of mild severity (based on the DSM-5 criteria)
The secondary objective of this substudy is to assess the concordance between positivity or negativity on CSF A?1?42 testing at entry in Study WN28745 and amyloid PET visual read in the WN28745-PET substudy. |
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E.3 | Principal inclusion criteria |
- Adult patients, 50 to 90 years of age, inclusive - Clinical diagnosis of probable mild Alzheimer disease based on NINCDS/ADRDA criteria - Availability of a person ('caregiver') who in the investigator's judgment has frequent and sufficient contact with the patient, and is able to provide accurate information regarding the patient's cognitive and functional abilities - Fluency in the language of the tests used at the study site - Willingness and ability to complete all aspects of the study - Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted) - If currently receiving approved medications for AD, doses must have been stable for at least 5 months prior to randomization |
?Tener entre 50 y 90 años de edad, ambos inclusive ?Diagnóstico clínico de EA leve probable, basándose en los criterios NINCDS/ADRDA ?Contar con una persona (?cuidador?) que, de acuerdo con el criterio del investigador, mantenga un contacto frecuente y suficiente con el paciente, y sea capaz de proporcionar información exacta con respecto a las capacidades cognitivas y funcionales del paciente. ?Dominar el idioma de los test utilizados en el centro del estudio ?Disposición y capacidad para completar todos los aspectos del estudio ?Agudeza visual y auditiva suficiente (está permitido el uso de gafas graduadas y audífonos) para realizar los test neuropsicológicos, de acuerdo con el criterio del investigador ?En el momento de la inclusión en el estudio, estará permitido el uso de medicaciones para la EA aprobadas siempre que los pacientes estén recibiendo una dosis y una pauta posológica estable 5 meses antes de la randomización. |
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E.4 | Principal exclusion criteria |
- Dementia or NCD due to a condition other than AD, including, but not limited to, frontotemporal dementia, Parkinson disease, dementia with Lewy bodies, Huntington disease, or vascular dementia - History or presence of clinically evident vascular disease potentially affecting the brain that in the opinion of the investigator has the potential to affect cognitive function - History or presence of stroke within the past 2 years or documented history of transient ischemic attack within the last 12 months - History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits - History of schizophrenia, schizoaffective disorder, or bipolar disorder - Alcohol and/or substance abuse or dependence (according to the DSM-5) within the past 2 years (nicotine use is allowed) - History or presence of atrial fibrillation - Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, angina pectoris, cardiac failure New York Heart Association Class II or higher) - Uncontrolled hypertension - Chronic kidney disease - Impaired hepatic function |
- Demencia o NCD debidos a trastornos distintos de la EA, incluyendo, aunque no exclusivamente, demencia frontotemporal, enfermedad de Parkinson, demencia con cuerpos de Lewy, enfermedad de Huntington o demencia vascular - Antecedentes o presencia de enfermedades vasculares clínicamente evidentes que afecten potencialmente al cerebro que, en opinión del investigador, tengan el potencial de afectar a la capacidad cognitiva - Antecedentes o presencia de ictus en los 2 últimos años o antecedentes documentados de ataque isquémico transitorio en los 12 últimos meses - Antecedentes o presencia de trastornos autoinmunes sistémicos que causen potencialmente enfermedad neurológica progresiva asociada a déficits cognitivos - Antecedentes de esquizofrenia, trastornos esquizoafectivos o trastornos bipolares - Abuso o dependencia de alcohol y/o sustancias tóxicas (de acuerdo con DSM-5) en los 2 últimos años (está permitido el uso de nicotina) - Antecedentes o presencia de fibrilación auricular - Enfermedades cardiovasculares inestables o clínicamente significativas en los 2 últimos años - Hipertensión no controlada - Enfermedad renal crónica - Deterioro de la función hepática |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in Alzheimer's Disease Activity Scale-Cognitive subscale 13 (ADAS-Cog13) scores
Mean change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores |
Cambio medio con respecto al valor basal en la puntuación ADAS Cog13
Cambio medio con respecto al valor basal en la puntuación ADCS-ADL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- from baseline to Week 104 |
- desde el período basal hasta la semana 104 |
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E.5.2 | Secondary end point(s) |
- Change in biomarkers (t-tau, p-tau, Abeta 1-42 levels) in cerebral spinal fluid - Change in MRI volumetry, assessed on structural MRI - Change in Clinical Dementia Rating (CDR-SB/CDR-GS) - Change in neuropsychiatric behaviour: Neuropsychiatric Inventory (NPI) total and domain scores - Change in cognition: MMSE total score - Safety: Incidence of adverse events, serious adverse events and treatment discontinuations |
- Cambio en biomarcadores en el LCR, en las concentraciones de t-tau, p-tau y Abeta1-42 - Cambio en la volumetría en RM, evaluada en una RM estructural - Cambio en CDR-SB/CDR-GS - Cambio en la conducta neuropsiquiátrica: Puntuación total y de los dominios del NPI - Cambio en la función cognitiva: Puntuación total del MMSE - Seguridad: Incidencia de acontecimientos adversos, de acontecimientos adversos graves y de suspensión del tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- from baseline to Week 104 - from baseline to Week 104 - from baseline to Week 104 - from baseline to Week 104 - from baseline to Week 104 - 152 weeks |
- desde el período basal hasta la semana 104 - desde el período basal hasta la semana 104 - desde el período basal hasta la semana 104 - desde el período basal hasta la semana 104 - desde el período basal hasta la semana 104 - 152 semanas |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers, exploratory biomarkers, clinical genotyping, imaging. |
Biomarcadores, biomarcadores exploratorios, genotipos clínicos, imágenes. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Bulgaria |
Canada |
Denmark |
France |
Italy |
Japan |
Netherlands |
Portugal |
Sweden |
Argentina |
Australia |
Brazil |
Czech Republic |
Finland |
Germany |
Guatemala |
Hungary |
Korea, Republic of |
Spain |
Mexico |
Poland |
Russian Federation |
Switzerland |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date when the last patient, last visit (LPLV) occurs or the date on which the last datapoint required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later. |
La terminación del estudio se define como la fecha en la que tiene lugar la última visita del último paciente (UVUP) o la fecha en la que se reciben los últimos datos del último paciente requeridos para el análisis estadístico o para el seguimiento de la seguridad, dependiendo de la que sea posterior. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |